5H94

Crystal structure of Swine MHC CLASSI for 1.48 angstroms

Summary for 5H94

• Entry DOI: 10.2210/pdb5h94/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, Nonapeptide from Influenza A virus HA protein, ... (4 entities in total)
• Functional Keywords: swine; crystal structure; mhc i; influenza a virus; mechanism; ctl immunity, immune system
• Biological source: Sus scrofa (Pig); More
• Cellular location: Secreted : Q07717
• Total number of polymer chains: 6
• Total formula weight: 88331.60

Authors

Fan, S.,Zhang, N.,Wang, S.,Wu, Y.,Xia, C. (deposition date: 2015-12-25, release date: 2016-05-18, Last modification date: 2024-11-06)

Primary citation

Fan, S.,Wu, Y.,Wang, S.,Wang, Z.,Jiang, B.,Liu, Y.,Liang, R.,Zhou, W.,Zhang, N.,Xia, C.
Structural and Biochemical Analyses of Swine Major Histocompatibility Complex Class I Complexes and Prediction of the Epitope Map of Important Influenza A Virus Strains
J.Virol., 90:6625-6641, 2016

PubMed Abstract: The lack of a peptide-swine leukocyte antigen class I (pSLA I) complex structure presents difficulties for the study of swine cytotoxic T lymphocyte (CTL) immunity and molecule vaccine development to eliminate important swine viral diseases, such as influenza A virus (IAV). Here, after cloning and comparing 28 SLA I allelic genes from Chinese Heishan pigs, pSLA-3*hs0202 was crystalized and solved. SLA-3*hs0202 binding with sβ2m and a KMNTQFTAV (hemagglutinin [HA]-KMN9) peptide from the 2009 pandemic swine H1N1 strain clearly displayed two distinct conformations with HA-KMN9 peptides in the structures, which are believed to be beneficial to stimulate a broad spectrum of CTL immune responses. Notably, we found that different HA-KMN9 conformations are caused, not only by the flexibility of the side chains of residues in the peptide-binding groove (PBG), but also by the skewing of α1 and α2 helixes forming the PBG. In addition, alanine scanning and circular-dichroism (CD) spectra confirmed that the B, D, and F pockets play critical biochemical roles in determining the peptide-binding motif of SLA-3*hs0202. Based on biochemical parameters and comparisons to similar pockets in other known major histocompatibility complex class I (MHC-I) structures, the fundamental motif for SLA-3*hs0202 was determined to be X-(M/A/R)-(N/Q/R/F)-X-X-X-X-X-(V/I) by refolding in vitro and multiple mutant peptides. Finally, 28 SLA-3*hs0202-restricted epitope candidates were identified from important IAV strains, and two of them have been found in humans as HLA-A*0201-specific IAV epitopes. Structural and biochemical illumination of pSLA-3*hs0202 can benefit vaccine development to control IAV in swine.

PubMed: 27170754
DOI: 10.1128/JVI.00119-16

Experimental method

X-RAY DIFFRACTION (1.48 Å)